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Published October 11, 2011 | Published
Journal Article Open

Thermodynamic basis for the genome to capsid charge relationship in viral encapsidation


We establish an appropriate thermodynamic framework for determining the optimal genome length in electrostatically driven viral encapsidation. Importantly, our analysis includes the electrostatic potential due to the Donnan equilibrium, which arises from the semipermeable nature of the viral capsid, i.e., permeable to small mobile ions but impermeable to charged macromolecules. Because most macromolecules in the cellular milieu are negatively charged, the Donnan potential provides an additional driving force for genome encapsidation. In contrast to previous theoretical studies, we find that the optimal genome length is the result of combined effects from the electrostatic interactions of all charged species, the excluded volume and, to a very significant degree, the Donnan potential. In particular, the Donnan potential is essential for obtaining negatively overcharged viruses. The prevalence of overcharged viruses in nature may suggest an evolutionary preference for viruses to increase the amount of genome packaged by utilizing the Donnan potential (through increases in the capsid radius), rather than high charges on the capsid, so that structural stability of the capsid is maintained.

Additional Information

© 2011 by the National Academy of Sciences. Edited by David A. Tirrell, California Institute of Technology, Pasadena, CA, and approved August 26, 2011 (received for review June 9, 2011). Published online before print October 3, 2011. Z.-G.W. and C.L.T. acknowledge support from the Jacobs Institute for Molecular Engineering for Medicine at Caltech. C.L.T. is thankful for financial support from an National Institute of Health (NIH)training grant. Author contributions: J.W. and Z.-G.W. designed research; C.L.T. and Z.-G.W. performed research; C.L.T. and Z.-G.W. analyzed data; and C.L.T. and Z.-G.W. wrote the paper. The authors declare no conflict of interest. This Direct Submission article had a prearranged editor.

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